Fabry disease is a multisystem disorder associated with wide variability in clinical expression.
Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of
alpha-galactosidase A. The
enzyme defect leads to the systemic accumulation of
glycosphingolipids with alpha-galactosyl moieties consisting predominantly of
globotriaosylceramide,
galabiosylceramide and two additional
glycosphingolipids. Four hemizygotes patients with a family history of
Fabry disease and deficiency of the
enzyme alpha-galactosidase A were selected. Each patient received purified
alpha-galactosidase by
intravenous infusion (0.2 mg/kg). The infusion was administered every 2 weeks, for 40 min, for a total of 12 months. Outcome measures include
neurological manifestations (acroparaesthesia,
hypohidrosis, vasomotion), kidney function, cardiac manifestations,
angiokeratomas, and
corneal dystrophy.
alpha-Galactosidase A prepared from human fibroblast is safe and well tolerated. After 12 months of
therapy the mean
creatinine clearance increased, there was significant improvement in the acroparaesthesias and in the
hypohidrosis. Physical stigmata, such as
angiokeratomas in the skin, and characteristic benign corneal abnormalities remained stable.
Enzyme replacement therapy would therefore represent a significant advance in treatment of patients with
Fabry disease.
Enzyme replacement therapy is safe and likely to improve the prognosis of
Fabry disease.